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Higher Midazolam Cl...
Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults
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- van Rongen, Anne (författare)
- St Antonius Hosp, Dept Clin Pharm, Koekoekslaan 1, NL-3435 CM Nieuwegein, Netherlands;Leiden Univ, Leiden Acad Ctr Drug Res, Div Pharmacol, Leiden, Netherlands;Reinier de Graaf Hosp, Dept Clin Pharm, Delft, Netherlands
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- Brill, Margreke JE (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,St Antonius Hosp, Dept Clin Pharm, Koekoekslaan 1, NL-3435 CM Nieuwegein, Netherlands;Leiden Univ, Leiden Acad Ctr Drug Res, Div Pharmacol, Leiden, Netherlands
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- Vaughns, Janelle D. (författare)
- Childrens Natl Hlth Syst, Div Anesthesiol & Pain Med, Washington, DC USA;Childrens Natl Hlth Syst, Div Clin Pharmacol, Washington, DC USA
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- Valitalo, Pyry A. J. (författare)
- Leiden Univ, Leiden Acad Ctr Drug Res, Div Pharmacol, Leiden, Netherlands
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- van Dongen, Eric P. A. (författare)
- St Antonius Hosp, Dept Anesthesiol & Intens Care, Nieuwegein, Netherlands
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- van Ramshorst, Bert (författare)
- St Antonius Hosp, Dept Surg, Nieuwegein, Netherlands
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- Barrett, Jeffrey S. (författare)
- Childrens Hosp Philadelphia, Lab Appl PK PD, Philadelphia, PA 19104 USA
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- van den Anker, Johannes N. (författare)
- Childrens Natl Hlth Syst, Div Clin Pharmacol, Washington, DC USA;Univ Childrens Hosp, Div Pediat Pharmacol & Pharmacometr, Basel, Switzerland;Sophia Childrens Univ Hosp, Erasmus MC, Intens Care, Rotterdam, Netherlands;Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Surg, Rotterdam, Netherlands
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- Knibbe, Catherijne A. J. (författare)
- St Antonius Hosp, Dept Clin Pharm, Koekoekslaan 1, NL-3435 CM Nieuwegein, Netherlands;Leiden Univ, Leiden Acad Ctr Drug Res, Div Pharmacol, Leiden, Netherlands
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(creator_code:org_t)
- 2017-08-07
- 2018
- Engelska.
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 57:5, s. 601-611
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- BackgroundThe clearance of cytochrome P450 (CYP) 3A substrates is reported to be reduced with lower age, inflammation and obesity. As it is unknown what the overall influence is of these factors in the case of obese adolescents vs. morbidly obese adults, we studied covariates influencing the clearance of the CYP3A substrate midazolam in a combined analysis of data from obese adolescents and morbidly obese adults.MethodsData from 19 obese adolescents [102.7 kg (62-149.5 kg)] and 20 morbidly obese adults [144 kg (112-186 kg)] receiving intravenous midazolam were analysed, using population pharmacokinetic modelling (NONMEM 7.2). In the covariate analysis, the influence of study group, age, total body weight (TBW), developmental weight (WTfor age and length) and excess body weight (WTexcess = TBW - WTfor age and length) was evaluated.ResultsThe population mean midazolam clearance was significantly higher in obese adolescents than in morbidly obese adults [0.71 (7%) vs. 0.44 (11%) L/min; p < 0.01]. Moreover, clearance in obese adolescents increased with TBW (p < 0.01), which seemed mainly explained by WTexcess, and for which a so-called 'excess weight' model scaling WTfor age and length to the power of 0.75 and a separate function for WTexcess was proposed.Discussion We hypothesise that higher midazolam clearance in obese adolescents is explained by less obesity-induced suppression of CYP3A activity, while the increase with WTexcess is explained by increased liver blood flow. The approach characterising the influence of obesity in the paediatric population we propose here may be of value for use in future studies in obese adolescents.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
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